Acetylsalicylic acid (ASA) was first synthesized by Charles Gerhardt in 1853. However, Gerhardt did not pursue his invention. Bayer commercialized crystalline acetylsalicylic acid in 1899 under the trade name ASPIRIN. U.S. Pat. No. 644,077 for the crystalline acetylsalicylic acid was granted in 1900 to Felix Hoffmann, a Bayer chemist. Until recently, the original crystalline form, known as Form I, was the only known crystalline form of aspirin and the only form of aspirin that is stable at room temperature. As reported in Chemical & Engineering News, Nov. 21, 2005, Zaworotko et al., J. Am. Chem. Soc., 2005, 127, 16802, reported the synthesis of a second polymorphic form of aspirin. Aspirin Form II is kinetically stable at 100 K (−173° C.), but converts back to Form I at ambient conditions
Amorphous glass aspirin has also been formed. However, except possibly for some microscopic residues, amorphous aspirin has been produced only at very low temperatures. Above the glass transition temperature of about 243 Kelvin (−30° C.), amorphous aspirin converts rapidly to the crystalline Form I. Thus, all prior art forms of aspirin convert to Form I at room temperature. As a result of the low temperature required to create and maintain the amorphous form, there has been essentially no practical application of the amorphous solid state form.
Johari et al., Physical Chemistry Chemical Physics, 2000, 2, 5479-5484, report the vitrification of aspirin by melting and cooling and by ball-milling at ambient temperature to form a vitreous or supercooled viscous liquid aspirin that is stable against crystallization for several days at 298K. The viscous liquid was found to flow slowly when tilted in a container, but did not crystallize for four to five days at 298K. The vitreous aspirin samples did ultimately undergo complete crystallization, which was accelerated when the samples were kept at about 340K.
Johari et al. report that the vitreous state has a higher energy state than the crystal state with a lower frequency of its phonon modes and a greater anharmonicity that make absorption and assimilation directly from the solid state more effective and efficient. In its bulk form, the vitreous aspirin is reported to dissolve more slowly than the same mass of finely powdered crystals of aspirin. As is well known in the art, a bulk sample of a substance has a significantly smaller surface area than finely powdered crystals. That makes the dissolution of the bulk form much more difficult, accounting for the slower dissolution rate of the bulk vitreous aspirin reported by Johari et al.